The invention relates to the coalescence of fluorinated oligomers and therapeutic agents as self assembled coatings and formulations, and their use in drug delivery.
Localized therapeutic delivery, including therapies that control the proliferation or growth of tissue into the open path of blood vessels, has been achieved with implantable devices such as drug eluting stents (DES). However, these devices are imperfect and can result in frequent side effects. The presence of residual foreign material can elicit a damaging inflammatory response and induce coagulation. Various techniques can be employed to modify the surface of implantable devices to improve biocompatibility and thromboresistance as well as impart properties different from those of the device material, e.g., infection resistance (i.e., via the delivery of a biologically active agent), radiopacity, conductivity, etc. In the DES arena, these techniques have had limited success.
Transient medical devices, i.e., devices that reside in the body for very short periods of time (inserted and removed) can also be used as localized therapeutic delivery vehicles. The use of a transient medical device (e.g., balloon catheter, guidewire, syringe needle, or probes) would be more advantageous over permanent, implantable medical devices as there are no long term biocompatibility issues.
As a result of the issues associated with DES, the concept of using a drug eluting balloon (DEB) catheter to locally deliver an anti-restenotic drug, such as paclitaxel, at the site of arterial disease is now seen as an opportunity to provide an alternative treatment which circumvents many of the concerns associated with DES. The DEB catheter would deliver a therapeutic amount of drug effectively upon inflation while in contact with the lumen wall for a limited time.
The DEB catheter approach has been the subject of several clinical trials since 2006. However, the outcome of many of these trials, including several repeated by the same companies with slightly reformulated materials, has been one of limited successes, due to inherent limitations in the carrier molecules for the drugs. The general strategy has been to coat the balloon catheter with established dye agents or pharmaceutical emulsifying materials that have an established regulatory history (see U.S. Patent Publication No. 20060020243). The result is a less than optimal performance in terms of retention onto the balloon during intra-luminal delivery (e.g., 90% of drug can be lost even before reaching the targeted tissues, with some absorbed into the balloons, and <6% being transferred to the diseased tissue) (see Axel De Labriolle et al., Catheterization and Cardiovascular Interventions 73:643 (2009)).
These results demonstrate a need for a synthetic modular approach to address the limitations of drug retention with efficient and preferential transfer of drug into the local tissues. To address these imitations, the carrier molecule needs to be designed with low blood activation with reduced local delivery of the carrier system upon arrival of the balloon at the target site.